Integrated protein network and microarray analysis

Authors: Yvan Devaux Francisco Azuaje Mélanie Vausort Céline Yvorra Daniel R Wagner

Publish Date: 2010/04/23

Volume: 10, Issue: 3, Pages: 329-337

PDF Link

Abstract

A significant proportion of patients develop left ventricular LV dysfunction and heart failure HF after acute myocardial infarction MI Existing biomarkers of HF provide limited information after MI To identify new prognostic biomarkers in MI patients we designed an approach combining protein interaction networks and microarray analysis of blood cells Blood samples for RNA and protein analysis were taken from 127 acute MI patients Echocardiography was performed at one month Assuming that angiogenesis is related to cardiac repair after MI a proteinprotein interaction network of angiogenesis was constructed and analyzed Among the 556 proteins and 686 interactions of this network a cluster of 53 proteins highly specialized in regulation of cell growth was identified Of these 53 proteins 38 were found differentially expressed by microarrays between low ≤ 40 and high 40 LV ejection fraction EF patients n = 32 Among these 38 genes prediction analysis identified a set of three genes able to predict significant LV dysfunction EF ≤ 40 with an area under the receiver operating characteristic curve AUC of 082 These three genes—vascular endothelial growth factor B thrombospondin1 and placental growth factor—had a stronger predictive value than brain natriuretic peptide and troponin T AUC of 063 Independent validations on protein expression and quantitative PCR datasets confirmed the results In conclusion a new strategy is described that allows identifying new potential biomarkers The three specific biomarkers described here remain to be validated in a larger patient populationThe authors thank Céline Jeanty Malou Gloesener and Loredana Jacobs for expert technical assistance We also thank Dr Georges Gilson Laboratory of Biochemistry Centre Hospitalier Luxembourg for NTproBNP assessment This work was supported by grants from the Society for Research on Cardiovascular Diseases the National Funds for Research and the Ministry of Culture Higher Education and Research of Luxembourg

Keywords: